Prokinetics Prescribing in Paediatrics: Evidence on Cisapride, Domperidone, and Metoclopramide

Objectives: Domperidone and metoclopramide are prokinetics commonly prescribed off-label to infants and younger children in an attempt to treat gastro-oesophageal reflux symptoms. Another prokinetic drug, cisapride, was used but withdrawn in 2000 in the United Kingdom because of serious arrhythmic adverse events. Medicines and Healthcare Products Regulatory Agency issued safety warnings for domperidone in May 2012 and restricted its indications. We report here national primary care prescribing trends and safety signals of these drugs in children. Methods: We used data from the General Practice Research Database between 1990 and 2006 for children <18 years. Descriptive statistics and Poisson regressions were performed to characterise prescribing trends. We examined safety signals in nested case–control studies. Results: The proportion of children <2 years old being prescribed one of the medications doubled during the study period. Prescriptions of domperidone increased 10-fold, mainly following the withdrawal of cisapride in 2000. Prescriptions of metoclopramide did not change significantly. Despite the increase in prescriptions of domperidone, no new safety signals were identified. Conclusions: These data showed dramatic changes in prescribing of cisapride and domperidone despite the lack of good-quality supporting evidence. It is possible that these prescribing trends were influenced by published guidelines. Even if produced without robust efficacy and safety evidence, published guidelines can influence clinicians and consequently affect prescribing. Therefore, improving the evidence base on prokinetics to inform future guidelines is vital. The lack of new safety signals during this period would support the development of suitable powered clinical studies

Systematic Review on the Functional Status of Elderly Hip Fracture Patients using Katz Index of Activity of Daily Living (Katz ADL) Score

Hip fractures cases are common in elderly population. After a hip fracture, around 80% of patients were unable to carry out at least one independent activity of daily living (ADL). This review attempted to provide an evidence-based literature on ADL of elderly hip fracture patients. A computerised literature search using Medline (OVID) and Scopus databases were conducted to identify relevant studies on ADL of elderly hip fracture patients that was assessed with Katz ADL score. Only articles that fulfilled the inclusion criteria were included in this review. Initial search identified 314 potentially relevant articles but after careful screening, only 5 full-text articles were selected for the present review. Three studies showed an increase dependent level of the patients’ ADL after hip fractures. Two studies showed not more than half of the patients were unable to regain their pre-fracture ADL level after one year of hip fracture incidence. Feeding/eating showed the highest independent activity while bathing was the lowest independent activity among patients. In conclusion, elderly hip fracture patients have declined ADL with the risk that they may never regain their pre-fracture ADL level

The effect of increasing the supply of skilled health providers on pregnancy and birth outcomes: evidence from the midwives service scheme in Nigeria

Background: Limited availability of skilled health providers in developing countries is thought to be an important barrier to achieving maternal and child health-related MDG goals. Little is known, however, about the extent to which scaling-up supply of health providers will lead to improved pregnancy and birth outcomes. We study the effects of the Midwives Service Scheme (MSS), a public sector program in Nigeria that increased the supply of skilled midwives in rural communities on pregnancy and birth outcomes. Methods: We surveyed 7,104 women with a birth within the preceding five years across 12 states in Nigeria and compared changes in birth outcomes in MSS communities to changes in non-MSS communities over the same period. Results: The main measured effect of the scheme was a 7.3-percentage point increase in antenatal care use in program clinics and a 5-percentage point increase in overall use of antenatal care, both within the first year of the program. We found no statistically significant effect of the scheme on skilled birth attendance or on maternal delivery complications. Conclusion: This study highlights the complexity of improving maternal and child health outcomes in developing countries, and shows that scaling up supply of midwives may not be sufficient on its own

Declining uncertainty in transient climate response as CO2 forcing dominates future climate change

Carbon dioxide has exerted the largest portion of radiative forcing and surface temperature change over the industrial era, but other anthropogenic influences have also contributed. However, large uncertainties in total forcing make it difficult to derive climate sensitivity from historical observations. Anthropogenic forcing has increased between the Fourth and Fifth Assessment Reports of the Intergovernmental Panel of Climate Change (IPCC; refs,), although its relative uncertainty has decreased. Here we show, based on data from the two reports, that this evolution towards lower uncertainty can be expected to continue into the future. Because it is easier to reduce air pollution than carbon dioxide emissions and because of the long lifetime of carbon dioxide, the less uncertain carbon dioxide forcing is expected to become increasingly dominant. Using a statistical model, we estimate that the relative uncertainty in anthropogenic forcing of more than 40% quoted in the latest IPCC report for 2011 will be almost halved by 2030, even without better scientific understanding. Absolute forcing uncertainty will also decline for the first time, provided projected decreases in aerosols occur. Other factors being equal, this stronger constraint on forcing will bring a significant reduction in the uncertainty of observation-based estimates of the transient climate response, with a 50% reduction in its uncertainty range expected by 2030

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

High grade angiosarcoma arising in fibroadenoma

Primary angiosarcoma of the breast is a rare tumour that account for fewer than 0.05% of all malignant mammary tumours. Angiosarcoma may have an perfidious clinical onset. Radiologic findings are often nonspecific and may appear completely normal in one-third of cases with primary angiosarcoma. The prognosis is usually poor because of the high rates of local recurrence and early development of metastases. Aggressive surgical resection is the mainstay of treatment. The role of adjuvant therapy has not yet been well established